Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hilgendorf, I; Gerhardt, LM; Tan, TC; Winter, C; Holderried, TA; Chousterman, BG; Iwamoto, Y; Liao, R; Zirlik, A; Scherer-Crosbie, M; Hedrick, CC; Libby, P; Nahrendorf, M; Weissleder, R; Swirski, FK.
Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium.
CIRC RES. 2014; 114(10): 1611-1622.
Doi: 10.1161/CIRCRESAHA.114.303204
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- Co-Autor*innen der Med Uni Graz
- Zirlik Andreas
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- Abstract:
- Healing after myocardial infarction involves the biphasic accumulation of inflammatory lymphocyte antigen 6C (Ly-6C)(high) and reparative Ly-6C(low) monocytes/macrophages (Mo/MΦ). According to 1 model, Mo/MΦ heterogeneity in the heart originates in the blood and involves the sequential recruitment of distinct monocyte subsets that differentiate to distinct macrophages. Alternatively, heterogeneity may arise in tissue from 1 circulating subset via local macrophage differentiation and polarization. The orphan nuclear hormone receptor, nuclear receptor subfamily 4, group a, member 1 (Nr4a1), is essential to Ly-6C(low) monocyte production but dispensable to Ly-6C(low) macrophage differentiation; dependence on Nr4a1 can thus discriminate between systemic and local origins of macrophage heterogeneity. This study tested the role of Nr4a1 in myocardial infarction in the context of the 2 Mo/MΦ accumulation scenarios. We show that Ly-6C(high) monocytes infiltrate the infarcted myocardium and, unlike Ly-6C(low) monocytes, differentiate to cardiac macrophages. In the early, inflammatory phase of acute myocardial ischemic injury, Ly-6C(high) monocytes accrue in response to a brief C-C chemokine ligand 2 burst. In the second, reparative phase, accumulated Ly-6C(high) monocytes give rise to reparative Ly-6C(low) F4/80(high) macrophages that proliferate locally. In the absence of Nr4a1, Ly-6C(high) monocytes express heightened levels of C-C chemokine receptor 2 on their surface, avidly infiltrate the myocardium, and differentiate to abnormally inflammatory macrophages, which results in defective healing and compromised heart function. Ly-6C(high) monocytes orchestrate both inflammatory and reparative phases during myocardial infarction and depend on Nr4a1 to limit their influx and inflammatory cytokine expression.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, Ly - blood
- Antigens, Ly - physiology
- Cell Movement - physiology
- Female -
- Inflammation - metabolism
- Inflammation - pathology
- Inflammation Mediators - metabolism
- Inflammation Mediators - physiology
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Monocytes - metabolism
- Monocytes - pathology
- Myocardial Infarction - blood
- Myocardial Infarction - pathology
- Myocardial Infarction - prevention & control
- Nuclear Receptor Subfamily 4, Group A, Member 1 - blood
- Nuclear Receptor Subfamily 4, Group A, Member 1 - physiology
- Find related publications in this database (Keywords)
- hormone receptors
- nuclear
- macrophages
- monocytes
- myocardial infarction